Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis.

BACKGROUND & AIMS: We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism. METHODS: We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells. RESULTS: Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes. CONCLUSIONS: Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.

Physiological Demands of Elite Cross-Country Skiing During a Real Competition.

The aim of this study was to assess different physiological variables before and after a 5-km (women) and 10-km (men) cross-country skiing competition to determine potential mechanisms of fatigue. Fourteen elite-level skiers competed in an official cross-country skiing competition using the classical style (9 men and 5 women). Instantaneous skiing velocity was measured during the race by means of 15-Hz global positioning system devices. Before and after the race, a sample of venous blood was obtained to assess changes in blood lactate and serum electrolyte and myoglobin concentrations. Prerace to postrace changes in blood oxygen saturation, forced vital capacity during a spirometry test, jump height during a countermovement jump, and handgrip force were also measured. Mean race speed was 15.8 ± 2.5 and 15.4 ± 1.5 km·h, whereas mean heart rate was 171 ± 6 and 177 ± 3 b·min for men and women, respectively. There were no significant prerace to postrace changes in jump height, handgrip force, and forced vital capacity in men and women. Blood oxygen saturation was reduced from prerace to postrace in men (95.9 ± 2.1% to 93.1 ± 2.3%, p = 0.02) and women (97.8 ± 1.1% to 92.4 ± 2.1%, p < 0.01), whereas blood lactate concentration increased at the end of the race in men (1.4 ± 0.5 to 4.9 ± 2.1 mmol·L, p < 0.01) and women (1.9 ± 0.1 to 6.9 ± 3.2 mmol·L, p < 0.01). After the race, blood markers of muscle damage were at low concentrations, whereas serum electrolytes remained unchanged. Fatigue in 5- and 10-km cross-country skiing competitions was related to a reduced blood oxygen carrying capacity and presumably increased muscle and blood acidosis, whereas the influence of exercise-induced muscle damage on fatigue was minor.

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis.

OBJECTIVE: Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. DESIGN: Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. RESULTS: Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. CONCLUSIONS: p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis.

The biliary epithelium gives rise to liver progenitor cells.

UNLABELLED: Severe liver diseases are characterized by expansion of liver progenitor cells (LPC), which correlates with disease severity. However, the origin and role of LPC in liver physiology and in hepatic injury remains a contentious topic. We found that ductular reaction cells in human cirrhotic livers express hepatocyte nuclear factor 1 homeobox B (HNF1ß). However, HNF1ß expression was not present in newly generated epithelial cell adhesion molecule (EpCAM)-positive hepatocytes. In order to investigate the role of HNF1ß-expressing cells we used a tamoxifen-inducible Hnf1ßCreER/R26R(Yfp/LacZ) mouse to lineage-trace Hnf1ß(+) biliary duct cells and to assess their contribution to LPC expansion and hepatocyte generation. Lineage tracing demonstrated no contribution of HNF1ß(+) cells to hepatocytes during liver homeostasis in healthy mice or after loss of liver mass. After acute acetaminophen or carbon tetrachloride injury no contribution of HNF1ß(+) cells to hepatocyte was detected. We next assessed the contribution of Hnf1ß(+) -derived cells following two liver injury models with LPC expansion, a diethoxycarbonyl-1,4-dihydro-collidin (DDC)-diet and a choline-deficient ethionine-supplemented (CDE)-diet. The contribution of Hnf1ß(+) cells to liver regeneration was dependent on the liver injury model. While no contribution was observed after DDC-diet treatment, mice fed with a CDE-diet showed a small population of hepatocytes derived from Hnf1ß(+) cells that were expanded to 1.86% of total hepatocytes after injury recovery. Genome-wide expression profile of Hnf1ß(+) -derived cells from the DDC and CDE models indicated that no contribution of LPC to hepatocytes was associated with LPC expression of genes related to telomere maintenance, inflammation, and chemokine signaling pathways. CONCLUSION: HNF1ß(+) biliary duct cells are the origin of LPC. HNF1ß(+) cells do not contribute to hepatocyte turnover in the healthy liver, but after certain liver injury, they can differentiate to hepatocytes contributing to liver regeneration.

Acute consumption of a caffeinated energy drink enhances aspects of performance in sprint swimmers.

This study investigated the effect of a caffeinated energy drink on various aspects of performance in sprint swimmers. In a randomised and counterbalanced order, fourteen male sprint swimmers performed two acute experimental trials after the ingestion of a caffeinated energy drink (3 mg/kg) or after the ingestion of the same energy drink without caffeine (0 mg/kg; placebo). After 60 min of ingestion of the beverages, the swimmers performed a countermovement jump, a maximal handgrip test, a 50 m simulated competition and a 45 s swim at maximal intensity in a swim ergometer. A blood sample was withdrawn 1 min after the completion of the ergometer test. In comparison with the placebo drink, the intake of the caffeinated energy drink increased the height in the countermovement jump (49.4 (SD 5.3) v. 50.9 (SD 5.2) cm, respectively; P<0.05) and maximal force during the handgrip test with the right hand (481 (SD 49) v. 498 (SD 43) N; P<0.05). Furthermore, the caffeinated energy drink reduced the time needed to complete the 50 m simulated swimming competition (27.8 (SD 3.4) v. 27.5 (SD 3.2) s; P<0.05), and it increased peak power (273 (SD 55) v. 303 (SD 49) W; P <0.05) and blood lactate concentration (11.0 (SD 2.0) v. 11.7 (SD 2.1) mM; P<0.05) during the ergometer test. The caffeinated energy drink did not modify the prevalence of insomnia (7 v. 7%), muscle pain (36 v. 36%) or headache (0 v. 7%) during the hours following its ingestion (P>0.05). A caffeinated energy drink increased some aspects of swimming performance in competitive sprinters, whereas the side effects derived from the intake of this beverage were marginal at this dosage.

CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis.

OBJECTIVE: Chemokines are known to play an important role in the pathophysiology of alcoholic hepatitis (AH), a form of acute-on-chronic liver injury frequently mediated by gut derived lipopolysaccharide (LPS). In our study, we hypothesise that chemokine CCL20, one of the most upregulated chemokines in patients with AH, is implicated in the pathogenesis of AH by mediating LPS induced liver injury. DESIGN: CCL20 gene expression and serum levels and their correlation with disease severity were assessed in patients with AH. Cellular sources of CCL20 and its biological effects were evaluated in vitro and in vivo in chronic, acute and acute-on-chronic experimental models of carbon tetrachloride and LPS induced liver injury. RNA interference technology was used to knockdown CCL20 in vivo. RESULTS: CCL20 hepatic and serum levels were increased in patients with AH and correlated with the degree of fibrosis, portal hypertension, endotoxaemia, disease severity scores and short term mortality. Moreover, CCL20 expression was increased in animal models of liver injury and particularly under acute-on-chronic conditions. Macrophages and hepatic stellate cells (HSCs) were identified as the main CCL20 producing cell types. Silencing CCL20 in vivo reduced LPS induced aspartate aminotransferase and lactate dehydrogenase serum levels and hepatic proinflammatory and profibrogenic genes. CCL20 induced proinflammatory and profibrogenic effects in cultured primary HSCs. CONCLUSIONS: Our results suggest that CCL20 upregulation is strongly associated with LPS and may not only represent a new potential biomarker to predict outcome in patients with AH but also an important mediator linking hepatic inflammation, injury and fibrosis in AH.

Semaphorin 7A contributes to TGF-ß-mediated liver fibrogenesis.

Semaphorin7A (SEMA7A) is a membrane-anchored protein involved in immune and inflammatory responses, exerting an effect on pulmonary fibrosis. Thus, we aimed to investigate the role of SEMA7A in hepatic fibrosis. Liver injury was induced in vivo by carbon tetrachloride i.p. injection or bile duct ligation in wild-type and SEMA7A knockout (KO) mice. Human and mouse liver samples and primary mouse hepatic cell populations were used for Western blot analysis, quantitative real-time RT-PCR, and immunohistochemistry. SEMA7A is highly expressed in hepatic stellate cells (HSCs). The expression of SEMA7A and its receptor ß1-integrin subunit increase during liver injury and in activated HSCs. Transforming growth factor ß-stimulated HSCs showed increased expression of SEMA7A in a SMAD2/3-independent manner, leading to increased expression of fibrogenic and inflammation markers. This pattern was significantly blunted in SEMA7A KO HSCs. Overexpression of SEMA7A in HSCs showed increased fibrogenic and inflammation markers expression. In vivo, SEMA7A KO mice treated with carbon tetrachloride and bile duct ligation developed reduced fibrosis versus wild-type mice. Moreover, SEMA7A expression increased in liver samples of patients with fibrosis versus healthy controls. SEMA7A was expressed in the liver and was increased in the course of liver fibrosis, both in mice and in humans. SEMA7A was mainly expressed in HSCs with respect to other cell types in the liver and plays a critical role in regulating fibrosis.

A caffeinated energy drink improves jump performance in adolescent basketball players.

This study aimed at investigating the effects of a commercially available energy drink on shooting precision, jump performance and endurance capacity in young basketball players. Sixteen young basketball players (first division of a junior national league; 14.9 ± 0.8 years; 73.4 ± 12.4 kg; 182.3 ± 6.5 cm) volunteered to participate in the research. They ingested either (a) an energy drink that contained 3 mg of caffeine per kg of body weight or (b) a placebo energy drink with the same appearance and taste. After 60 min for caffeine absorption, they performed free throw shooting and three-point shooting tests. After that, participants performed a maximal countermovement jump (CMJ), a repeated maximal jumps test for 15 s (RJ-15), and the Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). Urine samples were obtained before and 30 min after testing. In comparison to the placebo, the ingestion of the caffeinated energy drink did not affect precision during the free throws (Caffeine = 70.7 ± 11.8 % vs placebo = 70.3 ± 11.0 %; P = 0.45), the three-point shooting test (39.9 ± 11.8 vs 38.1 ± 12.8 %; P = 0.33) or the distance covered in the Yo-Yo IR1 (2,000 ± 706 vs 1,925 ± 702 m; P = 0.19). However, the energy drink significantly increased jump height during the CMJ (38.3 ± 4.4 vs 37.5 ± 4.4 cm; P < 0.05) mean jump height during the RJ-15 (30.2 ± 3.6 vs 28.8 ± 3.4 cm; P < 0.05) and the excretion of urinary caffeine (1.2 ± 0.7 vs 0.1 ± 0.1 µg/mL; P < 0.05). The intake of a caffeine-containing energy drink (3 mg/kg body weight) increased jump performance although it did not affect basketball shooting precision.

A 7-day oral supplementation with branched-chain amino acids was ineffective to prevent muscle damage during a marathon.

The aim of this study was to determine the effectiveness of a 7-day oral supplementation with branched-chain amino acids (BCAA) to prevent muscle damage during a marathon. Forty-six experienced runners were randomly divided into two groups, one with BCAA supplementation (n = 25, supplemented with 5 g day(-1) of powdered 1:0.5:0.5 leucine:isoleucine:valine, during the 7 days prior to the competition) and the other as a control group (n = 21, supplemented with an isocaloric placebo). Before the marathon race and within 3 min of finishing, leg muscle power was measured with a maximal countermovement jump and a urine sample was obtained. During the race, running pace was measured by means of a time-chip. Myoglobin concentration was determined in the urine samples as an indirect marker of muscle damage. A visual analog scale (0-10 points) was used to assess leg muscle pain during the race. In the BCAA group, the mean running pace during the marathon was similar to the control group (3.3 ± 0.4 vs. 3.3 ± 0.5 m s(-1), respectively, 0.98). The pre- to post-race reduction in muscle power was similar in both BCAA and control groups (-23.0 ± 16.1 vs. -17.3 ± 13.8 %, P = 0.13). Post-race urine myoglobin concentration was similar in both BCAA and control groups (5.4 ± 7.5 vs. 4.5 ± 8.6 µg mL(-1), P = 0.70). Finally, there were no differences between groups in the perceived muscle pain during the race (6 ± 1 vs. 5 ± 1 points, P = 0.80). A 7-day supplementation of BCAA (5 g day(-1)) did not increase the running performance during a marathon. Furthermore, BCAA supplementation was ineffective to prevent muscle power loss, muscle damage or perceived muscle pain during a marathon race.

Caffeine-containing energy drink improves physical performance in female soccer players.

There is little information about the effects of caffeine intake on female team-sport performance. The aim of this study was to investigate the effectiveness of a caffeine-containing energy drink to improve physical performance in female soccer players during a simulated game. A double-blind, placebo controlled and randomized experimental design was used in this investigation. In two different sessions, 18 women soccer players ingested 3 mg of caffeine/kg in the form of an energy drink or an identical drink with no caffeine content (placebo). After 60 min, they performed a countermovement jump (CMJ) and a 7 × 30 m sprint test followed by a simulated soccer match (2 × 40 min). Individual running distance and speed were measured using GPS devices. In comparison to the placebo drink, the ingestion of the caffeinated energy drink increased the CMJ height (26.6 ± 4.0 vs 27.4 ± 3.8 cm; P < 0.05) and the average peak running speed during the sprint test (24.2 ± 1.6 vs 24.5 ± 1.7 km/h; P < 0.05). During the simulated match, the energy drink increased the total running distance (6,631 ± 1,618 vs 7,087 ± 1,501 m; P < 0.05), the number of sprints bouts (16 ± 9 vs 21 ± 13; P < 0.05) and the running distance covered at >18 km/h (161 ± 99 vs 216 ± 103 m; P < 0.05). The ingestion of the energy drink did not affect the prevalence of negative side effects after the game. An energy drink with a dose equivalent to 3 mg of caffeine/kg might be an effective ergogenic aid to improve physical performance in female soccer players.

The use of energy drinks in sport: perceived ergogenicity and side effects in male and female athletes.

The use of caffeine containing energy drinks has dramatically increased in the last few years, especially in the sport context because of its reported ergogenic effect. The ingestion of low to moderate doses of caffeinated energy drinks has been associated with adverse side effects such as insomnia or increased nervousness. The aim of the present study was to assess psycho-physiological changes and the prevalence of side effects resulting from the ingestion of 3 mg caffeine/kg body mass in the form of an energy drink. In a double-blind and placebo controlled experimental design, ninety experienced and low-caffeine-consuming athletes (fifty-three male and thirty-seven female) in two different sessions were provided with an energy drink that contained 3 mg/kg of caffeine or the same decaffeinated energy drink (placebo; 0 mg/kg). At 60 min after the ingestion of the energy drink, participants completed a training session. The effects of ingestion of these beverages on psycho-physiological variables during exercise and the rate of adverse side effects were measured using questionnaires. The caffeinated energy drink increased self-perceived muscle power during exercise compared with the placebo beverage (6·41 (sd 1·7) v. 5·66 (sd 1·51); P= 0·001). Moreover, the energy drink produced a higher prevalence of side effects such as insomnia (31·2 v. 10·4 %; P< 0·001), nervousness (13·2 v. 0 %; P= 0·002) and activeness (16·9 v. 3·9 %; P= 0·007) than the placebo energy drink. There were no sex differences in the incidence of side effects (P>0·05). The ingestion of an energy drink with 3 mg/kg of caffeine increased the prevalence of side effects. The presence of these side effects was similar between male and female participants.

Compression stockings do not improve muscular performance during a half-ironman triathlon race.

PURPOSE: This study aimed at investigating the effectiveness of compression stockings to prevent muscular damage and preserve muscular performance during a half-ironman triathlon. METHODS: Thirty-six experienced triathletes volunteered for this study. Participants were matched for age, anthropometric data and training status and placed into the experimental group (N = 19; using ankle-to-knee graduated compression stockings) or control group (N = 17; using regular socks). Participants competed in a half-ironman triathlon celebrated at 29 ± 3 °C and 73 ± 8% of relative humidity. Race time was measured by means of chip timing. Pre- and post-race, maximal height and leg muscle power were measured during a countermovement jump. At the same time, blood myoglobin and creatine kinase concentrations were determined and the triathletes were asked for perceived exertion and muscle soreness using validated scales. RESULTS: Total race time was not different between groups (315 ± 45 for the control group and 310 ± 32 min for the experimental group; P = 0.46). After the race, jump height (-8.5 ± 3.0 versus -9.2 ± 5.3%; P = 0.47) and leg muscle power reductions (-13 ± 10 versus -15 ± 10 %; P = 0.72) were similar between groups. Post-race myoglobin (718 ± 119 versus 591 ± 100 µg/mL; P = 0.42) and creatine kinase concentrations (604 ± 137 versus 525 ± 69 U/L; P = 0.60) were not different between groups. Perceived muscle soreness (5.3 ± 2.1 versus 6.0 ± 2.0 arbitrary units; P = 0.42) and the rating of perceived effort (17 ± 2 versus 17 ± 2 arbitrary units; P = 0.58) were not different between groups after the race. CONCLUSION: Wearing compression stockings did not represent any advantage for maintaining muscle function or reducing blood markers of muscle damage during a triathlon event.

Influence of dorsiflexion shoes on jump performance.

The goal of dorsiflexion sports shoes is to increase jumping capacity by means of a lower position of the heel in relation to the forefoot which results in additional stretching of the ankle plantar flexors. The aim of this study was to compare a dorsiflexion sports shoe model with two conventional sports shoe models in a countermovement jump test. The sample consisted of 35 participants who performed a countermovement jump test on a force platform wearing the three models of shoes. There were significant differences in the way force was manifested (P<0.05) in the countermovement jump test, with a decrease in the velocity of the center of gravity and an increase in force at peak power and mean force in the concentric phase. Moreover, peak power was reached earlier with the dorsiflexion sports shoe model. The drop of the center of gravity was increased in CS1 in contrast to the dorsiflexion sports shoe model (P<.05). However, the dorsiflexion sports shoes were not effective for improving either peak power or jump height (P>.05). Although force manifestation and jump kinetics differ between dorsiflexion shoes and conventional sports shoes, jump performance was similar.

Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis.

OBJECTIVE: Alcoholic hepatitis (AH) is a severe clinical condition that needs novel therapies. The identification of targets for therapy is hampered by the lack of animal models of advanced AH. The authors performed a translational study through a transcriptome analysis in patients with AH to identify new molecular targets. DESIGN: Hepatic gene expression profiling was assessed by DNA microarray in patients with AH (n=15) and normal livers (n=7). Functional analysis was assessed by gene set enrichment analysis. Quantitative PCR was performed in patients with AH (n=40), hepatitis C (n=18), non-alcoholic steatohepatitis (n=20) and in mouse models of acute and chronic liver injury. Protein expression was assessed by immunohistochemistry and western blotting. RESULTS: Gene expression analysis showed 207 genes >5-fold differentially expressed in patients with AH and revealed seven pathways differentially regulated including 'cytokine-cytokine receptor interaction'. Several tumour necrosis factor (TNF) superfamily receptors, but not ligands, were overexpressed in AH. Importantly, Fn14 was the only TNF superfamily receptor exclusively upregulated in AH compared with other liver diseases and correlated with both 90-day mortality and severity of portal hypertension. Fn14 protein expression was detected in areas of fibrogenesis and in a population of hepatocytes. Fn14 expression was increased in experimental models of liver injury and was detected in progenitor cells. CONCLUSION: Translational research revealed that TNF superfamily receptors are overexpressed in AH. Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively upregulated in patients with AH. TNF superfamily receptors could represent a potential target for therapy.

Liver progenitor cell markers correlate with liver damage and predict short-term mortality in patients with alcoholic hepatitis.

UNLABELLED: Alcoholic hepatitis (AH) is a severe condition developed in patients with underlying alcoholic liver disease. Ductular reaction has been associated with chronic alcohol consumption but there is no information regarding the extent of liver progenitor cell (LPC) proliferation in AH. The aim of this study was to investigate LPC markers in AH and its correlation with disease severity. Fifty-nine patients with clinical and histological diagnosis of AH were included in the study. LPC markers were assessed by real-time polymerase chain reaction (PCR) and immunohistochemistry. Standard logistic regression analysis and classification and regression trees (CART) analysis were used for statistical analysis. A microarray analysis showed an up-regulation of LPC markers in patients with AH. Real-time PCR demonstrated that epithelial cell adhesion molecule (EpCAM), Prominin-1, and Keratin7 were significantly increased in patients with AH compared with normal livers (P ≤ 0.01), chronic hepatitis C (P ≤ 0.01), and HCV-induced cirrhosis (P ≤ 0.01). Immunohistochemistry scores generated for Keratin7 and EpCAM demonstrated a good correlation with gene expression. Keratin7 gene expression correlated with liver failure as assessed by model for endstage liver disease score (r = 0.41, P = 0.006) and Maddrey's discriminant function (r = 0.43, P = 0.004). Moreover, Keratin7 (OR1.14, P = 0.004) and Prominin-1 (OR1.14, P = 0.002), but not EpCAM (OR1.16, P = 0.06), were identified as independent predictors of 90-day mortality. CART analysis generated an algorithm based on the combination of Keratin7 and EpCAM gene expression that stratified three groups of patients with high, intermediate, and low short-term mortality (89%, 33%, and 6%, respectively; area under the receiver operating curve 0.73, 95% confidence interval 0.60-0.87). Keratin7 expression provided additional discrimination potential to the age, bilirubin, international normalization ratio, creatinine (ABIC) score. CONCLUSION: LPC markers correlate positively with severity of liver disease and short-term mortality in AH patients. This study suggests that LPC proliferation may be an important feature of AH pathophysiology.

Caffeine-containing energy drink improves sprint performance during an international rugby sevens competition.

The aim of this study was to determine the effects of a caffeine-containing energy drink on physical performance during a rugby sevens competition. A second purpose was to investigate the post-competition urinary caffeine concentration derived from the energy drink intake. On two non-consecutive days of a friendly tournament, 16 women from the Spanish National rugby sevens Team (mean age and body mass = 23 ± 2 years and 66 ± 7 kg) ingested 3 mg of caffeine per kg of body mass in the form of an energy drink (Fure(®), ProEnergetics) or the same drink without caffeine (placebo). After 60 min for caffeine absorption, participants performed a 15-s maximal jump test, a 6 × 30 m sprint test, and then played three rugby sevens games against another national team. Individual running pace and instantaneous speed during the games were assessed using global positioning satellite (GPS) devices. Urine samples were obtained pre and post-competition. In comparison to the placebo, the ingestion of the energy drink increased muscle power output during the jump series (23.5 ± 10.1 vs. 25.6 ± 11.8 kW, P = 0.05), running pace during the games (87.5 ± 8.3 vs. 95.4 ± 12.7 m/min, P < 0.05), and pace at sprint velocity (4.6 ± 3.3 vs. 6.1 ± 3.4 m/min, P < 0.05). However, the energy drink did not affect maximal running speed during the repeated sprint test (25.0 ± 1.5 vs. 25.0 ± 1.7 km/h). The ingestion of the energy drink resulted in a higher post-competition urine caffeine concentration than the placebo (3.3 ± 0.7 vs. 0.2 ± 0.1 µg/mL; P < 0.05). In summary, 3 mg/kg of caffeine in the form of a commercially available energy drink considerably enhanced physical performance during a women's rugby sevens competition.

Development of Seed-Oil Based Dried Sausages, Considering Physicochemical and Nutritional Quality and the Role of Food Neophobia.

A growing number of consumers now consider the consumption of processed meat products to be an essentially unhealthy habit. Hence, the reformulation of meat products is crucial. In this regard, the aim of this study is to reformulate "fuet", a traditional Spanish dried sausage, by replacing the pork fat with emulsified seed oils (50-50%, 25-75% and 0-100%). Four seed oils were evaluated, including commercial seeds (poppy and chia) and other seeds considered subproducts (melon and pumpkin). Physical parameters, nutritional quality and consumer evaluation of the reformulated dried sausages were analyzed. Additionally, we considered the effects of food neophobia on consumer evaluation. The resulting fuets had a higher concentration of linoleic and linolenic acids, which varied according to the oil used. In the sensory analysis, non-neophobic consumers showed higher preference for the reformulated fuets, while all consumers gave their highest ratings to the fuets produced with pumpkin seed oil.

Elaboration of Cookies Using Oils and Flours from Seeds and Nuts: Effects on Technological, Nutritional and Consumer Aspects.

The consumption of cookies is widely extended throughout the world, although their formulas contain ingredients such as saturated fats or refined flours that are considered harmful to health. In addition, cookies are generally made from wheat flour, and nowadays there is a growing concern about gluten intolerance, thus the demand for gluten-free products is increasing. In this regard, the aim of the present study is to reformulate traditional cookies by replacing wheat flour and butter by flours and oils from nuts and seeds. Within these seeds, poppy or chia are not commonly consumed ingredients as they can cause rejection by consumers. Thus, a study was performed to evaluate the neophobia level of consumers and the consumer acceptance for the inclusion of these novel ingredients in cookies. The results have been obtained by measuring physical parameters, proximate composition and consumer evaluation of five batches of cookies. By replacing butter and wheat flour with maize flour, almond, walnut, chia or poppy seed flours and oils, an increase of protein, fat and fiber has been observed as well as a decrease in carbohydrate content; thus, the resultant cookies would be a good source of vegetal protein as well as a source of oleic and linoleic acid with potential benefits on health. The cookies in general have similar physical properties and a positive consumer acceptance in texture, taste and external aspect. The Food Neophobia Scale results suggest that non-neophobic consumers gave higher scores than neophobic consumers in all the parameters. The resultant product would be a functional product able to substitute traditional ones not only directed to celiac people but all type of consumers because of their beneficial composition.

Differences in the Contractile Properties of the Biceps Femoris and Semitendinosus Muscles Throughout a Season in Professional Soccer Players.

The aim of this study was to monitor seasonal changes in the mechanical and neuromuscular characteristics of the knee flexor muscles with tensiomyography, the biceps femoris (BF) and semitendinosus (ST) muscles, of 27 soccer players. All male professional soccer players (age 25 ± 4 years) were measured at the beginning of the preseason (second week) and in the competitive season (10 weeks later). The variables contraction time (Tc) and muscle displacement (Dm) showed significant differences in some muscles, and in others they indicated a tendency to change. In general, the BF improved (more explosive and better muscle tone) and the ST worsened (slower and worse muscle tone) its values during the season. The findings of this study suggest that usual daily soccer training and weekly competition might produce antagonistic changes between the knee flexor muscles.

Effects of 3 mg/kg Body Mass of Caffeine on the Performance of Jiu-Jitsu Elite Athletes.

The effects of caffeine were investigated in judo, boxing, taekwondo and Brazilian jiu-jitsu. However, this substance was never investigated regarding traditional jiu-jitsu. Therefore, the aim of this research was to analyze the effects of caffeine in the Special Judo Fitness Test (SJFT) and technical variables during combat in traditional jiu-jitsu elite athletes. Methods: Twenty-two young professionals of traditional jiu-jitsu, 11 men and 11 women (age = 22 ± 4 (18−33) years, body mass = 66.6 ± 10.8 (46.2−86.1) kg, height = 1.70 ± 0.9 (1.55−1.85) m) with 15 ± 7 years of experience in traditional jiu-jitsu, participated in a double-blind, counterbalanced, crossover study. In two different conditions, the traditional jiu-jitsu athletes ingested 3 mg/kg body mass of caffeine or a placebo. After 60 min, they performed the SJFT test to measure throwing performance, and subsequently, combat to analyze offensive and defensive hitting techniques. Results: Caffeine had a main effect on the number of throws during the SJFT test (P < 0.01). In addition, it was effective in sets 2 (13 ± 2 vs. 14 ± 2; p = 0.01) and 3 (12 ± 2 vs. 13 ± 1; p = 0.03). There was also a main effect during the test on heart rate when caffeine was ingested (F = 12.48, p < 0.01). The effects of caffeine were similar compared to the placebo condition regarding performance during combat both in offensive and defensive fighting variables Conclusions: the pre-exercise ingestion of 3 mg/kg body mass of caffeine increased performance in the SJFT test, decreased fatigue perception, and increased power and endurance perception in professionally traditional jiu-jitsu athletes. However, it did not seem to improve offensive and defensive technical actions during combat.